The present invention relates to a bone graft composition in powder form and methods for its preparation and use. More particularly, the present invention is directed to non-immunogenic bone graft compositions in powder form comprising the tunica submucosa delaminated from the tunica muscularis and at least the luminal portion of the tunica mucosa of a segment of warm-blooded vertebrate intestine. Upon deposition into a damaged or defective region of bony tissue, the present bone graft powder compositions promote growth of endogenous tissue to repair the damaged or defective region.
It has been reported that compositions comprising the tunica submucosa and the basilar portions of the tunica mucosa of the intestine of warm-blooded vertebrates can be used as tissue graft materials in sheet form. See U.S. Pat. No. 4,902,508. The preferred compositions described and claimed in that patent are characterized by excellent mechanical properties, including high compliance, a high burst pressure point, and an effective porosity index which allowed such compositions to be used beneficially for vascular graft constructs. The graft materials disclosed in that patent are also useful in tendon and ligament replacement applications. When used in such applications the preferred graft constructs appear to serve as a matrix for the regrowth of the tissues replaced by the graft constructs.
Furthermore, it has been discovered that intestinal submucosa can be fluidized by comminuting and/or protease digestion, without loss of its apparent biotropic properties, for use in less invasive methods of administration (e.g., injection or topical) to host tissues in need of repair. See U.S. Pat. No. 5,275,826. Fluidized comminuted intestinal tissue comprising tunica submucosa has previously been successfully used to remodel damaged ligaments and tendons. Common events to this remodeling process include: widespread and very rapid neovascularization, proliferation of granulation mesenchymal cells, biodegradation of implanted SIS material, and lack of immune rejection.
The present application discloses methods for inducing the repair of bone in a warm-blooded vertebrates. The method comprising the step of implanting a bone graft composition, in powder form, into a site in need of repair under conditions conducive to the proliferation of endogenous tissues. The powder bone graft composition is formed from intestinal tissue of a warm-blooded vertebrate, the intestinal tissue comprising the tunica submucosa delaminated from the tunica muscularis and at least the luminal portion of the tunica mucosa, or a protease digest thereof.
Approximately 300,000 bone grafting and fracture repair procedures are performed each year in the United States. The market potential of an inexpensive, readily prepared and easily maintained bone graft material is estimated to be greater than 300 million dollars. Such biomaterials may be used to effectively repair fractures, craniofacial defects, periodontal defects, arthrodesis, and skeletal reconstruction following secondary bone loss to infection or neoplasm.
Currently, fresh autologous bone is the most effective bone graft material available. However, there are several disadvantages associated with the use of bone autografts including limited supply, the need for additional surgical procedures, and added morbidity associated with its harvest. Allogeneic bone grafts are also clinically used, but such graft compositions have serious shortcomings associated with their use, including the limited availability of cadaver bone, the quality of the banked bone, and the potential spread of human disease.
Ceramics, such as hydroxyapatite or tricalcium phosphate are also being investigated, but these materials are only osteoconductive rather than osteoinductive: i.e. new bone is generally only formed adjacent to the implant and the normal bone. More recently, a material known as Collagraft has been investigated as a potential bone graft material. It is a composite of bovine collagen, hydroxyapatite/tricalcium phosphate fibrillae ceramic, and bone marrow (aspirated from the iliac crest of the patient). The disadvantage of Collagraft is it lacks structural strength, and therefore is not useful in situations where cortical grafting is needed.
Because of the disadvantages associated with current bone repair therapeutic strategies, there is a strong need for alternative bone graft materials. It has been previously reported that compositions comprising tunica submucosa and basilar portions of the tunica mucosa of vertebrate intestine can be used as tissue graft materials which induce the growth of endogenous tissues. Applicants have discovered that powder forms of intestinal tissue comprising tunica submucosa and basilar portions of the tunica mucosa retain their biotropic properties and can be used as a bone graft material. As an alternative bone graft material, the present powder forms serve as a plentiful biological by-product that is inexpensive, readily prepared and easily maintained. This material induces and/or supports the regeneration of bony skeletal tissue, and preliminary results suggest that the structural and mechanical integrity of the grafted area is at least equivalent to that of the preexisting bone.
According to the present invention, a non-immunogenic bone graft composition in powder form is provided. In one embodiment the composition comprises lyophilized comminuted large or small intestinal tissue comprising the tunica submucosa delaminated from the tunica muscularis and at least the luminal portion of the tunica mucosa. In another aspect of the invention, there is provided a bone graft composition comprising lyophilized protease-digested intestinal tissue comprising the tunica submucosa delaminated from the tunica muscularis and at least the luminal portion of the tunica mucosa.
The described formulations have a variety of clinical uses in orthopedic surgery such as augmenting bony fusions, aiding in the repair of high-risk fractures, filling or bridging of bone defects, and assisting the attachment of metal or plastic prosthetic devices. In addition, they may be valuable in the treatment of periodontal disease, and in other tooth repair processes.
Furthermore, pharmaceuticals and bioactive agents can be admixed, coupled, or complexed with the bone graft compositions of this invention to create a composition for treating bone disorders locally.
In a preferred embodiment, the bone graft compositions described in this application are used advantageously in a method for inducing the repair of bone in a warm-blooded vertebrate. The method comprises the step of implanting a bone graft composition in powder form into the damaged or defective region, wherein the bone graft composition comprises the tunica submucosa and the basilar portions of the tunica mucosa of a segment of vertebrate intestine or a protease digest thereof. Most preferably the intestinal tissue consists essentially of the tunica submucosa, the muscularis mucosa and the stratum compactum of the tunica mucosa of warm-blooded intestinal tissue.
Additional objects, features, and advantages of the invention will become apparent to those skilled in the art upon consideration of the following detailed description of preferred embodiments exemplifying the best mode of carrying out the invention as presently perceived.